South Africa (SA) has the largest HIV epidemic globally, and is simultaneously affected by poverty, inequality, violence and other legacies of Apartheid. Children growing up in disadvantaged communities affected by HIV are at high risk for cognitive, behavioral, health and educational problems that, in turn, increase their risk of acquiring or transmitting HIV. This study has the long-term goal of halting the devastation of the HIV epidemic by intervening to promote better cognitive, behavioral, and psychosocial functioning of adolescents in SA. We will use a socio-ecological model with a life course perspective to prospectively investigate factors linked to drug use, binge drinking and unprotected sex including adolescent attributes such as executive function, and past and current family and contextual factors. The population-based Asenze cohort of 4-6 year old children and their primary caregiver, funded through R01 DA023697, will form the study sample. They reside in five disadvantaged areas in KwaZulu-Natal. The children, born between 2004 and 2006, were previously assessed at two time points on cognitive, bio- medical, and psychosocial functioning and their caregivers were interviewed about caregiver HIV, mental health, substance use, stress, support, household assets and household substance use. Over 25% of caregivers were HIV+; 9% reported binge drinking, 31% screened positive for a psychiatric disorder, over 30% had experienced partner violence and 17% reported that someone in the household had a drinking problem. Only 9% of households contained an adult who had completed secondary school. The Asenze cohort, reaching adolescence between 2017-2019, provides a unique opportunity to investigate the early-life origins of adolescent risk behavior in a disadvantaged population while building a strong foundation for later investigations into adulthood. We will investigate the pathways through which adolescent executive function and impulsivity, interact with both early and current social context (including their family adversity, disorganization and support as well as the behavior of their friends) affect the initiation of risky behaviors (drug use, binge drinking and unprotected sex). We will link the childhood cohort assessments of development and early adversity to those to be collected in both early and mid adolescence, including cognitive development, executive function and the initiation of risky behaviors. The findings will be crucial for informing critical prevention programs to halt the spread of HIV and promote healthy adolescent functioning. We will build research capacity through mentoring and training emerging South African scientists, masters, doctoral and post-doctoral students to build research expertise focused on investigating the impact of adolescent neurocognitive development on the initiation of risky behaviors, which result in negative education and sexual health outcomes, including HIV infection. We will also develop a SA research network of investigators working with cohort studies to promote their use in neuroscience and mental health outcomes.